Diverse Central Projection Patterns of Retinal Ganglion Cells

Cell Reports, Год журнала: 2017, Номер 18(8), С. 2058 - 2072

Опубликована: Фев. 1, 2017

Highlights•Anatomical characterization of Cre expression in the retina 88 driver lines•Morphological and histochemical classification Cre+ RGC types 26 lines•High resolution whole brain imaging labeled retinal axons reveals central targets•Correspondences described between line projection patternsSummaryUnderstanding how >30 ganglion cells (RGCs) mouse each contribute to visual processing will require more tools that label manipulate specific RGCs. We screened analyzed recombinase using transgenic lines. In many lines, was expressed multiple cell classes, but several exhibited selective expression. comprehensively mapped projections from RGCs lines viral tracers, high-throughput imaging, a data pipeline. identified over 50 retinorecipient regions present quantitative retina-to-brain connectivity map, enabling comparisons target-specificity across Projections two major targets were notably correlated: projecting outer shell or core lateral geniculate projected superficial deep layers within superior colliculus, respectively. Retinal images are available online at http://connectivity.brain-map.org.Graphical abstract

Язык: Английский

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Locally translated mTOR controls axonal local translation in nerve injury

Science, Год журнала: 2018, Номер 359(6382), С. 1416 - 1421

Опубликована: Март 22, 2018

How is protein synthesis initiated locally in neurons? We found that mTOR (mechanistic target of rapamycin) was activated and then up-regulated injured axons, owing to local translation messenger RNA (mRNA). This mRNA transported into axons by the cell size-regulating RNA-binding nucleolin. Furthermore, controlled axons. included regulation its own retrograde injury signaling molecules such as importin β1 STAT3 (signal transducer activator transcription 3). Deletion 3' untranslated region (3'UTR) mice reduced decreased after nerve injury. Both pharmacological inhibition deletion 3'UTR proprioceptive neuronal survival Thus, localization enables spatiotemporal control pathways regulating long-range intracellular signaling.

Язык: Английский

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Restoration of Visual Function by Enhancing Conduction in Regenerated Axons

Cell, Год журнала: 2016, Номер 164(1-2), С. 219 - 232

Опубликована: Янв. 1, 2016

Язык: Английский

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Precise temporal regulation of alternative splicing during neural development

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Май 31, 2018

Abstract Alternative splicing (AS) is one crucial step of gene expression that must be tightly regulated during neurodevelopment. However, the precise timing developmental switches and underlying regulatory mechanisms are poorly understood. Here we systematically analyze temporal regulation AS in a large number transcriptome profiles developing mouse cortices, vivo purified neuronal subtypes, neurons differentiated vitro. Our analysis reveals early-switch late-switch exons genes with distinct functions, these accurately define maturation stages. Integrative modeling suggests under direct combinatorial by sets RNA-binding proteins including Nova, Rbfox, Mbnl, Ptbp. Surprisingly, various subtypes sensory systems lack Nova and/or Rbfox expression. These retain “immature” program exons, affecting numerous synaptic genes. results provide new insights into organization neurodevelopmental transcriptome.

Язык: Английский

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Four alpha ganglion cell types in mouse retina: Function, structure, and molecular signatures

PLoS ONE, Год журнала: 2017, Номер 12(7), С. e0180091 - e0180091

Опубликована: Июль 28, 2017

The retina communicates with the brain using ≥30 parallel channels, each carried by axons of distinct types retinal ganglion cells. In every mammalian one finds so-called "alpha" cells (αRGCs), identified their large cell bodies, stout axons, wide and mono-stratified dendritic fields, high levels neurofilament protein. mouse, three αRGC have been described based on responses to light steps: On-sustained, Off-sustained, Off-transient. Here we employed a transgenic mouse line that labels αRGCs in live retina, allowing systematic targeted recordings. We characterize known identify fourth, On-transient responses. All four share basic aspects visual signaling, including receptive field center, weak antagonistic surround, absence any direction selectivity. They also distinctive waveform action potential, faster than other RGC types. Morphologically, they differ level stratification within IPL, which accounts for response properties. Molecularly, type has signature. A comparison across mammals suggests common theme, large-bodied split signal into channels arranged symmetrically respect polarity kinetics.

Язык: Английский

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Reaching the brain: Advances in optic nerve regeneration

Experimental Neurology, Год журнала: 2015, Номер 287, С. 365 - 373

Опубликована: Дек. 31, 2015

Язык: Английский

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Solving neurodegeneration: common mechanisms and strategies for new treatments

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Март 21, 2022

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.

Язык: Английский

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Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside

Annual Review of Cell and Developmental Biology, Год журнала: 2018, Номер 34(1), С. 495 - 521

Опубликована: Июль 25, 2018

After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure regenerate contrasts with axons' remarkable potential grow during embryonic development and after peripheral (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport trafficking, signaling transcription of regenerative programs, epigenetic modifications-control axon regeneration. In this review, we describe how manipulation intrinsic mechanisms elicits a response different organisms strategies are implemented form basis future treatment CNS injury.

Язык: Английский

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A Sensitized IGF1 Treatment Restores Corticospinal Axon-Dependent Functions

Neuron, Год журнала: 2017, Номер 95(4), С. 817 - 833.e4

Опубликована: Авг. 1, 2017

Язык: Английский

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Two Pairs of ON and OFF Retinal Ganglion Cells Are Defined by Intersectional Patterns of Transcription Factor Expression

Cell Reports, Год журнала: 2016, Номер 15(9), С. 1930 - 1944

Опубликована: Май 1, 2016

Visual information is conveyed to the brain by axons of >30 retinal ganglion cell (RGC) types. Characterization these types a prerequisite understanding visual perception. Here, we identify family RGCs that call F-RGCs on basis expression transcription factor Foxp2. Intersectional Foxp1 and Brn3 factors divides into four types, comprising two pairs, each composed closely related cells. One pair, F-mini(ON) F-mini(OFF), shows robust direction selectivity. They are among smallest in mouse retina. The other F-midi(ON) F-midi(OFF), larger not selective. Together, comprise >20% retina, halving number remain be classified doubling known direction-selective Co-expression Foxp genes also marks subsets macaques could primate homologs F-RGCs.

Язык: Английский

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